scholarly journals Hydrogen Sulfide-Evoked Intracellular Ca2+ Signals in Primary Cultures of Metastatic Colorectal Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3338
Author(s):  
Pawan Faris ◽  
Federica Ferulli ◽  
Mauro Vismara ◽  
Matteo Tanzi ◽  
Sharon Negri ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Hydrogen Sulfide ◽  
Transient Receptor Potential ◽  
Primary Cultures ◽  
Receptor Potential ◽  
Cell Types ◽  
Transient Receptor Potential Vanilloid ◽  
Sodium Hydrosulfide ◽  
Reverse Mode ◽  
Transient Receptor

Exogenous administration of hydrogen sulfide (H2S) is emerging as an alternative anticancer treatment. H2S-releasing compounds have been shown to exert a strong anticancer effect by suppressing proliferation and/or inducing apoptosis in several cancer cell types, including colorectal carcinoma (CRC). The mechanism whereby exogenous H2S affects CRC cell proliferation is yet to be clearly elucidated, but it could involve an increase in intracellular Ca2+ concentration ([Ca2+]i). Herein, we sought to assess for the first time whether (and how) sodium hydrosulfide (NaHS), one of the most widely employed H2S donors, induced intracellular Ca2+ signals in primary cultures of human metastatic CRC (mCRC) cells. We provided the evidence that NaHS induced extracellular Ca2+ entry in mCRC cells by activating the Ca2+-permeable channel Transient Receptor Potential Vanilloid 1 (TRPV1) followed by the Na+-dependent recruitment of the reverse-mode of the Na+/Ca2+ (NCX) exchanger. In agreement with these observations, TRPV1 protein was expressed and capsaicin, a selective TRPV1 agonist, induced Ca2+ influx by engaging both TRPV1 and NCX in mCRC cells. Finally, NaHS reduced mCRC cell proliferation, but did not promote apoptosis or aberrant mitochondrial depolarization. These data support the notion that exogenous administration of H2S may prevent mCRC cell proliferation through an increase in [Ca2+]i, which is triggered by TRPV1.

scholarly journals Bladder Dysfunction in an Obese Zucker Rat: The Role of TRPA1 Channels, Oxidative Stress, and Hydrogen Sulfide

2019 ◽  
Vol 2019 ◽  
pp. 1-12
Author(s):  
Igor Blaha ◽  
María Elvira López-Oliva ◽  
María Pilar Martínez ◽  
Paz Recio ◽  
Ángel Agis-Torres ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Sulfide ◽  
Transient Receptor Potential ◽  
Bladder Dysfunction ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Antioxidant Enzyme Activities ◽  
Zucker Rat ◽  
Obese Zucker Rat ◽  
Transient Receptor

Purpose. This study investigates whether functionality and/or expression changes of transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) channels, oxidative stress, and hydrogen sulfide (H2S) are involved in the bladder dysfunction from an insulin-resistant obese Zucker rat (OZR). Materials and Methods. Detrusor smooth muscle (DSM) samples from the OZR and their respective controls, a lean Zucker rat (LZR), were processed for immunohistochemistry for studying the expression of TRPA1 and TRPV1 and the H2S synthase cystathionine beta-synthase (CBS) and cysthathionine-γ-lyase (CSE). Isometric force recordings to assess the effects of TRPA1 agonists and antagonists on DSM contractility and measurement of oxidative stress and H2S production were also performed. Results. Neuronal TRPA1 expression was increased in the OZR bladder. Electrical field stimulation- (EFS-) elicited contraction was reduced in the OZR bladder. In both LZR and OZR, TRPA1 activation failed to modify DSM basal tension but enhanced EFS contraction; this response is inhibited by the TRPA1 blockade. In the OZR bladder, reactive oxygen species, malondialdehyde, and protein carbonyl contents were increased and antioxidant enzyme activities (superoxide dismutase, catalase, GR, and GPx) were diminished. CSE expression and CSE-generated H2S production were also reduced in the OZR. Both TRPV1 and CBS expressions were not changed in the OZR. Conclusions. These results suggest that an increased expression and functionality of TRPA1, an augmented oxidative stress, and a downregulation of the CSE/H2S pathway are involved in the impairment of nerve-evoked DSM contraction from the OZR.

scholarly journals Hydrogen sulfide induces hypersensitivity of rat capsaicin-sensitive lung vagal neurons: role of TRPA1 receptors

2013 ◽  
Vol 305 (7) ◽  
pp. R769-R779 ◽  
Author(s):  
Chun-Chun Hsu ◽  
Ruei-Lung Lin ◽  
Lu-Yuan Lee ◽  
You Shuei Lin
Keyword(s):  
Hydrogen Sulfide ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Right Atrial ◽  
Sodium Hydrosulfide ◽  
Lung Inflation ◽  
Baseline Activity ◽  
Intracellular Ca ◽  
Transient Receptor ◽  
Sensitizing Effect

The sensitization of capsaicin-sensitive lung vagal (CSLV) afferents by inflammatory mediators is important in the development of airway hypersensitivity. Hydrogen sulfide (H2S) is an endogenous mediator inducing hyperalgesia through transient receptor potential ankyrin 1 (TRPA1) receptors located on nociceptors. We conducted this study to determine whether H2S elevates the sensitivity of rat CSLV afferents. In anesthetized, artificially ventilated rats, the inhalation of aerosolized sodium hydrosulfide (NaHS, a H2S donor) caused no significant changes in the baseline activity of CSLV afferents. However, the afferent responses to right atrial injection of capsaicin or phenylbiguanide and to lung inflation were all markedly potentiated after NaHS inhalation. By contrast, the inhalation of its vehicle or NaOH (with a similar pH to NaHS) failed to enhance the afferent responses. Additionally, the potentiating effect on the afferent responses was found in rats inhaling l-cysteine (a substrate of H2S synthase) that slowly releases H2S. The potentiating effect of NaHS on the sensitivity of CSLV afferents was completely blocked by pretreatment of HC-030031 (a TRPA1 receptor antagonist) but was unaffected by its vehicle. In isolated rat CSLV neurons, the perfusion of NaHS alone did not influence the intracellular Ca2+ concentration but markedly potentiated the Ca2+ transients evoked by capsaicin. The NaHS-caused effect was totally abolished by HC-030031 pretreatment. These results suggest that H2S induces a nonspecific sensitizing effect on CSLV fibers to both chemical and mechanical stimulation in rat lungs, which appears mediated through an action on the TRPA1 receptors expressed on the nerve endings of CSLV afferents.

scholarly journals The transient receptor potential vanilloid-2 cation channel impairs glioblastoma stem-like cell proliferation and promotes differentiation

2012 ◽  
Vol 131 (7) ◽  
pp. E1067-E1077 ◽  
Author(s):  
Maria Beatrice Morelli ◽  
Massimo Nabissi ◽  
Consuelo Amantini ◽  
Valerio Farfariello ◽  
Lucia Ricci-Vitiani ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Cation Channel ◽  
Transient Receptor Potential Vanilloid ◽  
Transient Receptor

scholarly journals Blue Light Irradiation Induces Human Keratinocyte Cell Damage via Transient Receptor Potential Vanilloid 1 (TRPV1) Regulation

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Ju Ah. Yoo ◽  
Eunbi Yu ◽  
See-Hyoung Park ◽  
Sae Woong Oh ◽  
Kitae Kwon ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Blue Light ◽  
Transient Receptor Potential ◽  
Calcium Influx ◽  
Receptor Potential ◽  
Light Irradiation ◽  
Transient Receptor Potential Vanilloid ◽  
Skin Cells ◽  
Tnf Α ◽  
Transient Receptor

Although blue light has been reported to affect skin cells negatively, little is known about its action mechanisms in skin cells. Therefore, we investigated the role of the transient receptor potential vanilloid 1 (TRPV1) in blue light-induced effects on human keratinocytes and its underlying mechanisms. Blue light decreased cell proliferation and upregulated TRPV1 expression. Blue light also suppressed the epidermal growth factor receptor- (EGFR-) mediated signaling pathway by reducing the protein levels of EGFR and suppressing the EGFR/PI3K/AKT/GSK3β/FoxO3a pathway. The blue light-induced effect in cell proliferation was reversed by TRPV1 siRNA, but not capsazepine, a TRPV1-specific antagonist. In addition, blue light irradiation increased the production of reactive oxygen species (ROS) and tumor necrosis factor-α (TNF-α). Blue light irradiation also increased both phosphorylation levels of TRPV1 and calcium influx. The blue light-induced increase in production of ROS and TNF-α was reversed by capsazepine. Furthermore, the blue light-induced increase in production of TNF-α was attenuated by SP600125 or PDTC. These findings show that blue light regulates cell survival and production of ROS and TNF-α; its effects are mediated via TRPV1. Specifically, the effects of blue light on cell proliferation are mediated by upregulating TRPV1, a negative regulator of EGFR-FoxO3a signaling. Blue light-induced production of ROS and TNF-α is also mediated through increased calcium influx via TRPV1 activation.

scholarly journals Role of Transient Receptor Potential Vanilloid 4 Channel in Skin Physiology and Pathology

2020 ◽  
Vol 20 (2) ◽  
pp. 138
Author(s):  
Ammar Boudaka ◽  
Mallak Al-Yazeedi ◽  
Intisar Al-Lawati
Keyword(s):  
Transient Receptor Potential ◽  
Skin Barrier ◽  
Receptor Potential ◽  
Inflammatory Cells ◽  
Skin Inflammation ◽  
Cell Types ◽  
Transient Receptor Potential Vanilloid ◽  
Skin Physiology ◽  
Transient Receptor ◽  
Trpv4 Channel

Transient receptor potential vanilloid 4 (TRPV4) channel responds to temperature, as well as various mechanical and chemical stimuli. This non-selective cation channel is expressed in several organs, including the blood vessels, kidneys, oesophagus and skin. In the skin, TRPV4 channel is present in various cell types such as keratinocytes, melanocytes and sensory neurons, as well as immune and inflammatory cells, and engages in several physiological actions, from skin homeostasis to sensation. In addition, there is substantial evidence implicating dysfunctional TRPV4 channel—in the form of either deficient or excessive channel activity—in pathological cutaneous conditions such as skin barrier compromise, pruritus, pain, skin inflammation and carcinogenesis. These varied functions, combined with the fact that TRPV4 channel owns pharmacologically-accessible sites, make this channel an attractive therapeutic target for skin disorders. In this review, we summarize the different physiological and pathophysiological effects of TRPV4 in the skin.Keywords: TRPV4; Skin; Epidermis; Keratinocytes; Pain; Pruritis; Melanoma.

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